Biomedical subjects

M Owsianowski

Publications and source records attributed to M Owsianowski.

At least 19 recordsLinked to original sources

PubMed1992

The inhibitory effects of a positive inotropic quinolinone derivative, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), on bone-marrow progenitor cells and peripheral lymphocytes.

3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (OPC-8212) is a quinolinone derivative with positive inotropic properties. In order to elucidate the effect of OPC-8212 on the haemopoietic system we studied its in vitro effect on bone-marrow progenitor cells (granulocyte/monocyte colony-forming units [CFU-GM] and erythroid burst-forming units [BFU-E]), on the proliferation and secretion of granulocyte/monocyte colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) by peripheral lymphocytes, and on GM-CSF secretion by fibroblasts from healthy individuals. The dose-effect relations of OPC-8212 on CFU-GM proliferation and on lymphocytic GM-CSF secretion showed no effect at very low drug concentrations, with a threshold at the lower end of the therapeutic range and highly significant dose-dependent inhibition at concentrations above that threshold. BFU-E, peripheral lymphocyte proliferation and lymphocytic IFN-gamma secretion were depressed, although to a lesser extent, in a linear dose-dependent fashion. OPC-8212 did not affect GM-CSF secretion by one strain of fibroblasts but reduced it at higher concentrations in assays with another strain of cells. We conclude that direct toxic effects on bone-marrow progenitor cells, in combination with the inhibition of cytokines involved in the regulation of haemopoiesis in certain susceptible individuals, may be responsible for idiosyncratic reactions to OPC-8212.

Bone Marrow↗

PubMed1992

Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol.

The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon-gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF- or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production.

Acitretin↗

PubMed1991

Long-term cultured adult human keratinocytes secrete granulocyte-macrophage colony-stimulating factor but not interleukin-3 after cytokine exposure in vitro.

To investigate the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and of interleukin-3 (IL-3) by human keratinocytes in vitro, adult human keratinocytes (aHKc) from 3 different donors and a spontaneously transformed keratinocytic line (HaCaT) were cultured and exposed to various cytokines and to the protein kinase C-activating agent phorbol-12-myristate-13-acetate (PMA). GM-CSF and IL-3 were measured by highly specific and sensitive immunoassays. Our findings showed that long-term cultured aHKc and HaCaT cells are capable of secreting GM-CSF but not IL-3 upon cytokine and PMA stimulation. Both interleukin-1 and tumor necrosis factor alpha, which are known to be present in human epidermis, particularly during cutaneous inflammatory processes, were found to stimulate GM-CSF release. Therefore, we conclude that increased GM-CSF levels may play an important role in the interactions between epidermal keratinocytes and blood cells in vivo.

Adult↗

PubMed1990

Lymphokine release, suppressor cell generation, cell surface markers, and cytotoxic activity in cancer patients receiving natural interleukin-2.

We monitored patients treated for 5 days with continuous infusion of increasing doses (3 to 6 x 10(6) U/d) of natural interleukin-2 (IL-2). CD16+, CD25+, and CD56+ cells increased after treatment. Plasma tumor necrosis factor-alpha (TNF-alpha) levels, but not interferon-gamma (IFN-gamma) levels, increased during IL-2 treatment, but spontaneous and IL-2-stimulated TNF-alpha secretion in vitro remained abnormally low. However, mitogen-stimulated TNF-alpha release was normal. Mitogen-stimulated, but not IL-2-stimulated, IFN-gamma release was strongly depressed. Low spontaneous and IL-2-stimulated cytotoxicity on K562 or Daudi increased after treatment. Low suppressor cell generation also normalized after treatment. This appears to be the first reported study of immunologic monitoring of cancer patients treated with natural rather than recombinant IL-2.

Antigens, Differentiation↗

PubMed1982

[Nervous system diseases in large-city population. II. Effect of occupational factors].

The patients of a local outpatient department in a half--million population town have been examined. The rate of organic angiogenic encephalopathies, vasomotor headaches and epilepsy has been three times greater in those performing light work than in the hard-working group. No dependency between the hard work and rate of ischias and lumbago has been found. Operations of productive machines, similarly as the working place microclimatic conditions do not pose a risk of nervous system diseases, except ischias and lumbago which occur more frequently in an occupational group working at low temperature and considerable humidity or at an open air. Likewise, the body position at work significantly affects the rate of ischias and lumbago. Our findings prove that hard work does not pose an additional risk of nervous system diseases. Another conclusion of those investigations is that advantageous microclimate and body position at the working place, possibly accompanied by corrective physical training, are significant in the prevention of ischias and lumbago.

Adolescent↗

PubMed1978

[Nervous system diseases in workers of a large metallurgical plant. II. Impact of occupational factors].

Correlation between some factors connected with work performance in a big metallurgical plant, employing approximately 16000 persons, and the occurrence of nervous system diseases was analysed. It was found that among the most frequent diseases of nervous system cured in neurological dispensary of a big metallurgical plant are: ischias, epilepsy, syndrome of subjective ailments following a past cranio-cerebral trauma and vasomotor headaches. The studies performed did not reveal any clear correlation between the character and arduousness of work and the type of nervous system diseases occurring most frequently in a big industrial (metallurgical) plant. The prevalence of ischias is not significantly dependent on occupational factors. The possibility of continuation of work or necessity to stop working in result of a nervous system disease depend on the type of the disease.

Adult↗

PubMed1977

[Experiences in intensive therapy of apoplectiform pictures of cerebrovascular insufficiency].

Our observations indicate that attention should be paid primarily to the following, in the sequence given, when applying intensive therapy to patients suffering from apoplectiform phenomena of cerebro-vascular insufficiency: keep the respiratory passages open, prevent inflammatory processes, especially bronchopneumonia, give an optimum supply of calories, water and electrolyte to patients in the comatose state, compensate for disturbances in the central regulation of respiration and circulation, combat disturbances of the acid-base balance and prevent cerebral oedema and hyperthermia from central causes. The report was to emphasize the gasometric results of our studies which indicated that 65 per cent of the patients in this group suffer from significant hypoxia and that respiratory alkalosis occurred in 34 per cent. The cause seems to be a disturbance in the respiratory passages which leads to hyperventilation and to subsequent respiratory alkalosis.

Alkalosis, Respiratory↗

PubMed1971